Volume transmission signalling via astrocytes

Abstract

The influence of astrocytes on synaptic function has been increasingly studied, owing to the discovery of both gliotransmission and morphological ensheathment of synapses. While astrocytes exhibit at best modest membrane potential fluctuations, activation of G-protein coupled receptors (GPCRs) leads to a prominent elevation of intracellular calcium which has been reported to correlate with gliotransmission. In this review, the possible role of astrocytic GPCR activation is discussed as a trigger to promote synaptic plasticity, by affecting synaptic receptors through gliotransmitters. Moreover, we suggest that volume transmission of neuromodulators could be a biological mechanism to activate astrocytic GPCRs and thereby to switch synaptic networks to the plastic mode during states of attention in cerebral cortical structures.

Astrocytes regulate cortical state switching in vivo

“…What signals-neuronal or nonneuronal, intra-or extracellular, synchronized or desynchronized-cause the intracellular astrocytic Ca 2+ rises that occur before the state switch? There has been recent focus on mechanisms of focal Ca 2+ activation in astrocyte processes, both synaptic and nonsynaptic (30,33,34,47,62), but no broad consensus yet exists. G protein-coupled receptor (GPCR) activation and release of Ca 2+ from intercellular stores via IP 3 receptors is an accepted pathway for Ca 2+ increases in astrocyte somata (63,64), although it has recently been argued that this mechanism may not explain Ca 2+ increases in astrocyte processes (30).…”

Astrocytic control of synaptic function

“…Interestingly, neuromodulator signalling often relies on volume transmission that sets a long-range and long-lasting tone of neuromodulator, affecting many targets over prolonged periods of time [75]. The fact that astrocytes respond to neuromodulators therefore further illustrates how their action on synapses is mostly geared towards slower and more durable tuning of synaptic properties.…”

Septal Cholinergic Neuromodulation Tunes the Astrocyte-Dependent Gating of Hippocampal NMDA Receptors to Wakefulness

“…In these regions, the ACh tone fluctuates with changes in vigilance state: the highest levels are found during active wakefulness and the lowest during slow wave sleep (Marrosu et al, 1995; Lee et al, 2005; Zant et al, 2016). Interestingly, ACh is known to influence NMDAR activity and NMDAR-dependent functions (Kirkwood et al, 1999; Lin et al, 2013; Markram and Segal, 1990; Yang et al, 2013; Zappettini et al, 2014), and activates intracellular signaling in astrocytes through various ACh receptors (AChRs) (Hirase et al, 2014; Sharma and Vijayaraghavan, 2001; Shen and Yakel, 2012; Takata et al, 2011). Combined with evidence that ACh can promote D-serine synthesis and/or release (Lin et al, 2013; Singh et al, 2013; Takata et al, 2011), these data point to a link between vigilance state-dependent cholinergic activity and NMDAR co-agonist gating via astrocytic D-serine.…”

“…This makes astrocytes good candidates to receive, integrate and relay information about the neuromodulatory state of the brain, such that their impact on neuronal and brain function has become increasingly relevant in the scope of behavioral states (Chen et al, 2012; Ding et al, 2013; Hirase et al, 2014; Panatier at al., 2006; Schmitt et al, 2012; Paukert et al, 2014). This is supported by evidence that astrocytes are exquisite sensors of neuromodulators, such as norepinephrine and acetylcholine, that are involved in sensory modalities and vigilance states (Ding et al, 2013; Lee et al, 2005; Paukert et al, 2014; Pinto et al, 2013; Hirase et al, 2014; Navarrete et al, 2012; Sharma and Vijayaraghavan, 2001; Shen and Yakel, 2012; Takata et al, 2011). Here we used a variety of in vivo and in vitro approaches to examine fluctuations of endogenous D-serine availability throughout the day and their link with cholinergic activity.…”